The effect of human GH (hGH) on c-myc gene expression and cell proliferation in the Nb2 lymphoma cell line was examined. The addition of hormone to stationary cultures of Nb2 cells resulted in an increased accumulation of c-myc transcripts that was detectable within 15 min, reached a maximum induction of 25-fold in 3 h, and then gradually declined. Although maximal accumulation of c-myc transcripts occurred within 3 h after hGH addition, removal of the hormone even after 4 h of treatment resulted in a failure of the cells to proliferate. This loss of proliferative capacity following hormone removal was accompanied by a 20-fold reduction in the level of c-myc transcripts. These results indicate that hGH induced proliferation of Nb2 cells is associated with the induction and maintenance of c-myc gene expression.