Renal interstitial scarring is an important component of heroin-associated nephropathy. Kidney fibroblasts have been demonstrated to play a role in the development of renal scarring in a variety of renal diseases. We studied the effect of morphine, an active metabolite of heroin, on the proliferation of kidney fibroblasts. Morphine at a concentration of 10(-12) M enhanced (P < 0.001) the proliferation of kidney fibroblasts (control, 67.5 +/- 2.0 vs. morphine, 112.2 +/- 10.1 x 10(4) cells/well). [3H]thymidine incorporation studies further confirmed these results. Morphine at concentrations of 10(-12) M to 10(-10) M also modulated mRNA expression of early growth related genes (c-fos, c-jun and c-myc). Morphine at concentrations of 10(-8) to 10(-4) M promoted apoptosis of kidney fibroblasts and also enhanced the synthesis of p53 by kidney fibroblasts. We speculate that morphine-induced kidney fibroblast proliferation may be mediated through the activation of early growth related genes, whereas morphine induced kidney fibroblast apoptosis may be mediated through the generation of p53. The present in vitro study provides a hypothetical basis for the role of morphine in the development of renal interstitial scarring in patients with heroin-associated nephropathy.