The in vivo effect of a calf thymus extract (thymostimulin, TS) on the E-rosetting capacity, PHA blastogenic response, serum migration inhibitory activity (LIF) and skin reactivity to recall antigens was evaluated in 19 untreated patients with Hodgkin's disease. In patients the mean percentage of peripheral blood lymphocytes forming E-rosettes increased from 47 to 55.7% (P less than or equal to 0.001; normal: 58.9). The mean PHA stimulation index rose with all three concentrations tested but did not reach normal values. Serum LIF was positive in only one patient prior to treatment with a mean LIF for all patients of 0.75 (P less than or equal to 0.005). Skin tests were positive in ten patients (52.6%) prior to therapy and 18 patients following therapy (94.7%; P less than or equal to 0.05). Thymostimulin, in vivo, appears to return immunologic competency to a population of untreated patients with Hodgkin's disease.