A comparative study of lactogen receptors in lactogenic hormone-dependent (Nb2-11C) and independent (Nb2-SP) rat lymphoma cell lines revealed no significant differences in their binding and structural characteristics. The affinity for human growth hormone (hGH) and ovine prolactin is identical (K d) = 1.3 × 10−10M). Exposure to hGH results in a rapid receptor down-regulation. This process is faster in Nb2-SP cells, however, similar receptor levels are reached within 3 h. Affinity labeling revealed 2 major binding species (Mr 75 000 and 29000) in both cell lines. These observations suggest that the spontaneous proliferation of Nb2-SP cells probably results from an aberration in some post-receptoral event of the mitogenic pathway.