Previous reports have shown the capacity of diphenylhydantoin (DPH) to attach to the membranes of lymphatic cells as a hapten and thus exert an unspecific influence on their ability to express certain recognition molecules. This led us to the hypothesis, that DPH might as well serve to manipulate the t-helper-lymphocytes in a way that the mode of infection of these cells by the HIV might be blocked. In order to verify this hypothesis, we exposed normal control lymphocytes as well as lymphocytes from DPH-treated patients (3 X 100-150 mg DPH/day, Phenhydan, for a minimum of 10 days) to radioactively labeled HIV (125I). Remaining radioactivity was assessed using a gamma-counter and measured 64.000-92.000 counts/min (n = 24, mean 80.000) for the control lymphocytes, while remaining radioactivity for the DPH-treated lymphocytes ranged between 2000 and 7000 counts/min (n = 24, mean 4.000, p less than 0.001). These results and similar experiments obtained with FITC-labeled HIV led us to the conclusion that DPH inhibits HIV recognition of T-lymphocytes and therefore might be used in therapy and prophylaxis of AIDS.