The receptor binding, internalization and tyrosine kinase activation of insulin-like growth factors, IGF-I and IGF-II have been investigated in cultured adult bovine chromaffin cells. IGF-I receptor alpha-subunits (Mr approximately 130,000) bound IGF-I and IGF-II with identical affinity (Kd approximately 1 nM) and insulin with about 1000 times lower affinity. IGF-II receptors (Mr approximately 250,000) bound IGF-II with a Kd of 0.5 nM, IGF-I with about 10 times lower affinity and insulin with greater than 10,000 times lower affinity. The amounts of IGF-I and IGF-II receptors on the cell surface were 8 x 10(4) and 4 x 10(4) sites per cell, respectively. Insulin bound to a specific receptor with Kd approximately 2 nM and the amount of receptors was 1.5 x 10(4) sites per cell. IGF-I and IGF-II stimulated tyrosine kinase activity and autophosphorylation of the IGF-I receptor beta-subunit (Mr approximately 94,000) with equal potency (ED50 approximately 1 nM), whereas insulin was approximately 5 times less potent. Both IGF-I and IGF-II were internalized after their binding to cell surface receptors. Mannose-6-phosphate, which binds to the IGF-II receptor, did not alter the binding or internalization of IGF-II. It is concluded that IGF-I and IGF-II can exert their biological effects in chromaffin cells by activation of the IGF-I receptor tyrosine kinase or by interaction with the IGF-II receptor.