Insulin-like growth factor I (IGF-I) downregulates growth hormone (GH) expression in pituitary cell cultures. However, in vivo different results were found depending on the experimental protocol used. We determined the kinetics of changes of pituitary and serum GH concentrations after subcutaneous IGF-I administration (240 microg/100 g body weight) to rats every 12 h for various periods. These parameters were correlated with changes in the somatotroph cell population. A significant increase in serum GH was registered at 6 h after IGF-I injection. At this time, some somatotroph cells exhibited ultrastructurally signs of high secretory activity, whereas adjacent somatotroph cells showed a quiescent appearance with sizeable stores of secretory granules. In contrast, serum GH levels remained unchanged at 1, 2 and 12 h after each IGF-I injection. Pituitary GH concentrations were comparable to control levels during the first 48 h and declined significantly at 72 h and 96 h of IGF-I treatment. After these prolonged periods of time of treatment, the size and extension of organelles involved in protein synthesis decreased and mature secretory granules in the cytoplasm increased significantly in GH-secreting cells. The somatotroph cell density remained unchanged even at 96 h of treatment. In conclusion, our results suggest that periodical IGF-I administration to rats does not inhibit GH secretion. Interestingly, IGF-I injections induced early and significant increases in serum GH levels. This result may be a consequence of a temporary stimulatory action on somatotroph cells concurrent with increased secretory activity.