The experimental synergism of melphalan with DTIC and the ability of transfer factor to improve immunocompetence were the basis of an attempt to improve therapeutic results in disseminated malignant melanoma. Sixty-four evaluable patients with disseminated malignant melanoma were treated in a 21-day cycle as follows: DTIC 250 mg/M2 intravenously days 1 to 5, Connaught BCG 6 X 10(8) organisms on days 7, 12, and 17 by scarification, and transfer factor 1 unit (10(9) lymphocytes equivalent, from immunocompetent relatives of patients) subcutaneously on day 12, with or without L-PAM 30 mg/M2 on day 1. Twenty-nine patients received L-PAM and 35 did not. Remission rates of 17% and 23%, respectively, occurred in these groups. An additional 15 patients received DTIC-BCG and three doses of transfer factor on days 7, 12, and 17 and had a remission rate of 20%. Remission duration and survival were compared to historical controls of 111 patients treated with DTIC and 89 treated with DTIC-BCG. Median survival on DTIC-BCG-Transfer Factor was seven months compared to four months for DTIC (P = .003) but did not differ from DTIC-BCG. Addition of L-PAM did not improve remission duration or survival compared to DTIC-BCG but enhanced myelosuppression and immunosuppression. A 60% increase in delayed type hypersensitivity to recall antigens occurred in this study compared to 34% with DTIC-BCG (P = .005). Prognosis and immunocompetence were not directly related. In summary, in this study, (1) transfer factor therapy did not enhance the clinical effects of DTIC-BCG, although it augmented delayed type hypersensitivity to recall antigens; and (2) L-PAM was not additive to DTIC in the treatment of disseminated malignant melanoma and may have abrogated the effect of immunotherapy.