Vascular endothelial cell are closely related to vascular smooth muscle cells in structure and function. The interactions between them may play important roles in the modulation of function and structure of vascular wall. In the present study, the mitogenic regulations between cultured new bovine pulmonary arterial endothelial cell (PAEC) and pulmonary arterial smooth muscle (PASM) were investigated. When PAECs and PASMs were mixcultured, 3H-TdR incorporation into the mixed cells decreased significantly (P < 0.001 vs control). When PAECs and PASMs were cultured in conditioned medium from PASMs and PAECs respectively or they were cocultured, the proliferation of PAECs was inhibited while that of PASM was stimulated significantly (P < 0.05 vs control). It was also found that the concentration of cAMP increased but cGMP decreased in cocultured PASMs (P < 0.01 vs control), while the concentration of both cAMP and cGMP decreased significantly in cocultured PAECs (P < 0.01 vs control). These findings suggest that PAECs and PASMs may regulate their proliferation each other through the second messenger system.