Vastus lateralis muscle samples were obtained by needle biopsy from 18 healthy elderly men (65-82 yr) participating in a double blind, placebo (PL)-controlled trial of recombinant human GH (rhGH) and exercise and assessed for muscle morphology and skeletal muscle tissue expression of GH and insulin-like growth factors (IGFs). Subjects initially underwent progressive resistance training for 14 weeks and were then randomized to receive either rhGH (0.02 mg/kg BW.day, sc) or PL while undertaking a further 10 weeks of training. Muscle samples were obtained at baseline and at 14 and 24 weeks. The mean (+/- SEM) cross-sectional areas of type I and II fibers were similar (type I, 3891 +/- 167 microns2; type II, 3985 +/- 200 microns2) at baseline and increased (P < 0.01) by 16.2 +/- 4.1% and 11.8 +/- 3.8%, respectively, after the initial 14-week training period. After treatment (weeks 14-24), two-way repeated measures ANOVA revealed a main effect of time for type I (P < 0.01) and type II fibers (P < 0.05), but no group effect or interaction. The increase in cross-sectional area for the PL group was significant (P = 0.01) for type I (11.5 +/- 3.6%) and approached significance (P = 0.06) for type II fibers (11.1 +/- 5.6%). For rhGH, the change in type I (6.3 +/- 5.9%) and II (7.1 +/- 5.2%) fiber area was not significant. No apparent change in tissue GH receptor, IGF-I, IGF-I receptor, IGF-II, or IGF-II receptor messenger ribonucleic acids occurred as a result of exercise after the 14-week pretreatment period or after treatment with rhGH or PL. These results indicate that rhGH administration in exercising elderly men does not augment muscle fiber hypertrophy or tissue GH-IGF expression and suggests that deficits in the GH-IGF-I axis with aging do not inhibit the skeletal muscle tissue response to training.