In this pilot clinical investigation we have investigated the concept of modulating suppressor T lymphocyte (Ts) function to augment delayed type hypersensitivity (DTH) and antitumor immunity in patients with metastatic renal cell carcinoma. Cyclophosphamide (CY) was used for modulating Ts function. We used three doses of CY per 100 mg/m2, 500 mg/m2, and 1000 mg/m2. Cyclophosphamide was administered i.v. 24 h prior to the first of 6 weekly immunizations with irradiated autologous tumor cells mixed with Corynebacterium parvum. Twenty of 26 patients were evaluable for response. Five of these 20 (25%) evaluable patients had responses, one complete response and four partial responses. Fifteen patients had post-treatment skin testing with autologous tumor cells. Four of these 15 (26%) patients developed DTH to autologous tumor cells. Of the four patients acquiring skin test positivity three also had clinical responses, whereas among the 11 skin-test negative patients, only one clinical response was observed. Six of six (100%) patients who had serial T lymphocyte subset studies done had increases in their mean T helper/inducer:T suppressor/cytotoxic ratios after CY administration and immunization. These observations in an exploratory study suggest that further investigations of Ts modulation, autologous tumor cell skin testing, and T lymphocyte subsets may be of value.