A pharmacokinetic-pharmacodynamic study of a long-acting GH [Nutropin Depot; somatropin (rDNA origin) for injectable suspension] was performed in 25 patients with adult GH deficiency. Single doses of 0.25 mg/kg and 0.5 mg/kg, based on ideal body weight, were administered sc. After either dose, serum GH concentrations rose rapidly in both sexes. In men, the lower dose maintained serum IGF-I levels within 1 SD of the mean for age and sex for 14-17 d; the higher dose raised IGF-I levels 2 SD above the mean. In most women, all of whom were receiving oral estrogen, the lower dose did not normalize IGF-I levels; the higher dose maintained IGF-I near the mean for approximately 14 d. Increases in IGF binding protein-3 and acid-labile subunit levels were observed in both sexes; however, a sex-related difference was not obvious. Fasting glucose and insulin concentrations were transiently elevated in men receiving the higher dose. Patients tolerated the injections well. We concluded that a single injection of Nutropin Depot at these doses in patients with adult GH deficiency increased serum IGF-I to within normal limits for 14-17 d. Estrogen-treated women required approximately twice the dose needed in men to produce comparable IGF-I concentrations.