This study was undertaken to determine whether hormonal stimulation followed by chemotherapy with a cell-cycle specific agent would improve the effectiveness of the chemotherapy in a prostatic adenocarcinoma model. One hundred Copenhagen rats were randomised into 5 equal groups and injected subcutaneously with 2 x 10(7) cells of Dunning G strain prostatic adenocarcinoma. The groups were treated in the following fashion: 1. sham operated controls, 2. castration, 3. castration and methotrexate, 4. castration, testosterone and methotrexate and 5. castration and testosterone. When the tumours became palpable, all animals received the surgery to which they were randomised. Subsequent hormonal and chemotherapy was started 1 week thereafter. Therapy was given for 5 consecutive days followed by a 16-day recovery period and then continued in a cyclical fashion. Serial measurements of animal weights and tumour size were obtained. Analysis of tumour growth was restricted to the first 29 days of therapy because of a rapid decline in animal survival beyond that point. The group treated with castration, testosterone, and methotrexate inhibited tumour growth more than any other group and was the only group that was significantly different from control (P less than 0.05).