An elevation of intracellular cyclic adenosine 3', 5'-monophosphate (cAMP) is known to stimulate proliferation and expression of surface galactocerebroside (galC) in cultured Schwann cells from newborn rats and mice. We investigated the age-related differences in proliferative and differentiating responses of Schwann cells to forskolin, an adenylate cyclase activator, in mice at postnatal days (P) 3, 10 and 30. The proportion of surface galC-positive cells decreased progressively with time in all ages during the initial three days in vitro (DIV) but the proportion of Schwann cells expressing surface galC at P30 was lower than that at P3 or P10. Administration of 50 microM forskolin in the media on the four DIV induced surface galC expression in Schwann cells from P3 and P10 mice but not from P30 mice. Forskolin also stimulated the proliferation of Schwann cells from P3 and P10 mice in media containing 2% fetal bovine serum (FBS) but not those from P30 mice, which, however, proliferated in media containing 10% FBS. These results suggest that Schwann cells in suckling mice are more sensitive to cAMP in both proliferative and differentiating responses than in adult. These different responses in vitro may reflect differences in the intrinsic metabolic status of Schwann cells in vivo since myelin-forming Schwann cells proliferate actively prior to myelination but cease or become less active in proliferation once myelination progresses.