T-Lymphocyte responses in B-cell chronic lymphocytic leukemia (CLL) are abnormal by several criteria. We investigated the possibility that impaired T-cell responses might be due to increased suppressor cell activity by: (a) measuring the responses to phytohemagglutinin (PHA) stimulation of normal mononuclear cells cocultured with CLL lymphocytes compared to normal cells alone, (b) preincubation of lymphocytes in tissue culture medium prior to the addition of PHA, (c) measuring the responses of lymphocytes to PHA in the presence of indomethacin. Cells from 8 patients with CLL cocultured with normal cells did not suppress responses to PHA. Both preincubation in tissue culture medium and addition of indomethacin to the cell cultures have been shown to block different suppressor cell activities. As expected, both of these procedures significantly increased the PHA responses of lymphocytes from 7 normal individuals in contrast to essentially no change in the responses of lymphocytes from 9 and 11 patients with CLL. Since T cells are diluted by the predominant B lymphocytes in CLL, the mononuclear cells were fractionated with enrichment of T lymphocytes to 75–85%. No increases in PHA responses of the enriched T cells were observed after preincubation in two cases or with the addition of indomethacin in four cases. We were therefore unable to demonstrate global suppressor cell activity in CLL affecting PHA responses, and there was evidence of less than normal activity in two specific suppressor cell systems. We suggest that decreased T-cell responses to PHA in CLL represent an innate cellular abnormality.