Glomerular mesangial injury is the predominant renal lesion in patients with heroin addition. We studied the effect of morphine (an active metabolite of heroin)activated macrophages on mesangial cell (MC) proliferation and matrix synthesis. We prepared conditioned media containing either vehicle along (CSP), macrophage secretory products (MSP) and secretory products of morphine treated macrophages (M-MSP), M-MSP increased (P < 0.01) the proliferation of MC when compared with MSP alone. M-MSP increased synthesis of laminin by MC at concentrations of 10 to 50% when compared with cells treated with MSP alone (at 50% concentration, MSP, 126 +/- 19 vs. M-MSP, 312 +/- 14 ng/mg protein, P < 0.001). M-MSP also increased the synthesis of collagen type IV by MC. This effect of M-MSP was attenuated (P < 0.05) by anti-TGF-beta antibodies. Since M-MSP also increased mRNA expression for TGF-beta by MC, it appears that the effected of M-MSP on MC may be mediated through the generation of TGF-beta.