Forskolin and cAMP analogues (8-bromo cAMP and dibutyryl cAMP) induced proliferation or surface galC expression, depending on the concentrations, in rat and mouse Schwann cells in vitro. However, rat Schwann cells required much higher concentrations of these agents than mouse Schwann cells in both proliferation and surface galC expression. The concentrations needed for cellular proliferation were 0.5 microM forskolin or 10 microM cAMP analogues in mice and 2.5 microM forskolin or 50 microM cAMP analogues in rats. Surface galC was expressed in mouse Schwann cells at concentrations of 10 microM forskolin or 100 microM cAMP analogues, while in rat Schwann cells, 50 microM forskolin or 500 microM cAMP analogues was needed for expression of surface galC. Rat Schwann cells transformed from an elongated spindle shape to flattened cells by the addition of these agents. However, mouse Schwann cells remained spindle shaped and their processes were apparently elongated at concentrations of more than 1.0 microM forskolin or 100 microM cAMP analogues. These results may reflect the differences in the cellular metabolism between mouse and rat cells. Moreover, the elongation of mouse Schwann cell processes appeared to be associated with surface galC expression, suggesting that elongation may be an initial signal for differentiation in mouse Schwann cells.