Insulin-like growth factor-I (IGF-I) has been reported to mediate the effects of oestradiol-17 beta in the osteoblast-like osteosarcoma cell line ROS 17/2.8 and to stimulate directly cell proliferation in cell cultures derived from rat calvaria. Few data are available on the role of IGF-I in androgen stimulation of cultured skeletal cells and in oestrogen and androgen stimulation of bone and cartilage in vivo. The purpose of the present study was to compare the effect of IGF-I in rats in vivo with its effect in vitro on calvarial bone cells from females (responding only to oestrogens) and from males (responding only to androgens, such as testosterone and dihydrotestosterone). We found that IGF-I stimulated, in a dose- and time-dependent manner, the specific activity of creatine kinase (CK, a marker of skeletal cell division), in both female and male calvarial bone cells, in ROS 17/2.8 cells and in epiphyseal cartilage cell cultures. Maximal stimulation occurred at 30 or 100 nM within 1-2 h after stimulation. In ROS 17/2.8 cells, IGF-I stimulated [3H]thymidine incorporation, after 22 h of treatment, in parallel with CK activity. IGF-II, at higher doses than IGF-I (maximal stimulation at 300 nM), stimulated CK specific activity in female- and male-derived calvarial cell cultures. When IGF-I (50 nM) was applied together with oestradiol-17 beta (30 nM) or with dihydrotestosterone (300 nM) there was no additional response in the cultures.(ABSTRACT TRUNCATED AT 250 WORDS)