Osteoporosis is a debilitating and costly disease of the skeleton characterized by low bone mass and structural deterioration of bone tissue leading to bone fragility and an increased susceptibility to fractures of the hip, spine, and wrist. Current data suggest that at present time, 7.8 and 21.8 million women have osteoporosis and osteopenia respectively. The development of osteoporosis and related fracture in later life depends not only on the rate of bone loss in adulthood, but also on the amount of bone present at skeletal maturity. Oral contraceptives (OC), because of their capacity to diminish concentrations of free testosterone and estrogen, have been purported to affect bone mass in young adult women, but results have proven inconsistent. Further, positive skeletal effects of exercise training are thought to be compromised by use of OCs in skeletally immature females. PURPOSE: To assess the independent and synergistic effects of OC use on bone mineral density (BMD) and long bone mechanical bending stiffness (EI) in college-aged females after unilateral isokinetic resistance training. METHODS: Forty six females (age 20 +/- 1.4 yr, height 163.8 +/- 6.2cm, weight 58.9 +/- 8.6kg, fat 27.9 +/- 4.8%) were categorized as OC users (OC, N=22) or non-users (NOC, N=24). Subjects participated in 32 weeks (3 d/wk) of unilateral arm and leg training at an angular velocity of 60 degrees/s using isokinetic dynamometers. BMD and EIMRTA were assessed using dual-energy x-ray absorptiometry (DXA) and mechanical response tissue analysis (MRTA), respectively. RESULTS: Total leg and arm muscular strength of the trained limb increased by 16% and 15%, respectively (p < 0.001), beyond changes observed in the control limbs. Total body BMD increased from baseline for NOC subjects (p < 0.05), but not for OC users. This difference failed to show significance (p = 0.069) when comparisons were run between NOC and OC groups. Increases in ulnar BMD (p < 0.01 for all limbs) and BMD of the trained total hip (OC, p < 0.001; NOC, p < 0.05) occurred irrespective of contraceptive status. Positive changes in EI were conflicting, occurring in the trained ulna for the NOC group (p < 0.05), and trained tibia for OC users (p < 0.05). Tibial BMD increased only for the untrained leg in NOC subjects (p < 0.01). No between group differences were found to be significant, nor were differences between trained vs. untrained, and weight bearing (tibia) vs. non-weight-bearing (ulna) limbs found to be significant. CONCLUSION: These results suggest that oral contraceptives may limit attainment of total body peak bone mass in young adult females. Skeletal maturation in the ulna appeared to be unaffected by exercise training and OC use. Positive effects of exercise training on the total hip were seen in both groups, irrespective of OC status. Conversely, exercise training and use of OCs use may limit the attainment of bone mass in the tibia. Further studies are needed to determine the interactive effects of OC use and isokinetic resistance training on measures of total body and site-specific bone status.