There is a growing body of literature suggesting that some schizophrenic subjects have evidence of immune activation. One marker that has been consistently elevated in studies is the serum-soluble interleukin-2 receptor (SIL-2R). This article reports the results of 2 experiments: the first compares concentrations of serum SIL-2R in neuroleptic-naive schizophrenic patients and matched controls, and the second study contrasts serum SIL-2R concentrations in medicated schizophrenic subjects with and without tardive dyskinesia. Serum SIL-2R concentrations were elevated in neuroleptic-naive schizophrenic subjects as compared with controls (1705.7 (SD 1124.2) U/ml vs 739.8 (SD 325.5) U/ml). Medicated subjects with tardive dyskinesia had increased serum SIL-2R levels (2385.5 (SD 1822.0) U/ml) compared with medicated subjects without tardive dyskinesia (1259.6 (SD 1365.3) U/ml). Thus, elevations in serum SIL-2R levels are present prior to neuroleptic treatment, and there may be an association between serum SIL-2Rs and tardive dyskinesia.