Using the dimethylbenzanthracene-induced rat mammary tumor model, we examined the appearance and growth of tumors in animals given tamoxifen (TAM) either coincident with dimethylbenzanthracene or after initial tumor formation. While fewer tumors arose after coadministration of antiestrogen and carcinogen and TAM treatment caused regression of most existing tumors, new tumors developed in the presence of TAM in both studies. Since none of these new tumors regressed following ovariectomy, all were classified as hormone independent. Furthermore, these independent tumors grew more rapidly than both control-dependent and independent tumors, resulting in a greater average volume. These data suggest that a more aggressive form of hormone-independent tumor appears during TAM treatment.