Gelsolin, a regulator of the actin cytoskeleton, has been shown previously to act as a tumor suppressor in vitro and in vivo when introduced into certain cancer cell lines. To investigate the in vivo efficacy of gene therapy with the gelsolin gene, we inoculated nude mice with human urinary bladder cancer cells (UMUC-2 or DAB-1) and tested the effects of adding either retroviral DNA constructs containing gelsolin cDNA or retrovirus producer cells that produce the same retroviral constructs at high levels. The addition of retroviral gelsolin cDNA constructs did not inhibit tumor growth; however, this form of gene therapy, in which retrovirus producer cells were introduced, resulted in marked and reproducible tumor growth inhibition and prolonged survival time in the majority of animals tested. These findings demonstrate the potential for treating human urinary bladder carcinomas with the gelsolin gene.