Previous studies showed that VIP modulates mediators of two signal transduction pathways, namely the adenylate cyclase and the nonreceptor tyrosine protein kinase pp60c-src in cultured chick retinal pigment epithelium (RPE). Here we show that VIP modulates simultaneously two disparate cellular events, namely the cell proliferation and differentiation of the RPE, however, with different potencies. The maximal effects on proliferation and differentiation are observed at 5 x 10(-9)M and 5 x 10(-7)M, respectively. Treatment with the maximally effective concentrations of VIP for 10 days increases the cell numbers and the melanin contents to 150% and 200% of the controls, respectively. The lowest concentrations of VIP showing significant stimulatory effect on cell proliferation and melanin synthesis are 5 x 10(-11) M and 5 x 10(-9)M, respectively.