Eighteen newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) were divided into two groups based on the severity of the disease. Patients with very active disease were nonresponsive to skin test antigens used to assess delayed hypersensitivity. Skin test reactivity was intact in most patients with mildly active disease. Lymphocytes from subjects in both groups responded normally to phytohemagglutinin (PHA) when the results were expressed as counts per minute per million small lymphocytes. Serum from patients with severely active disease markedly suppressed lymphocyte responsiveness of autologous and allogeneic lymphocytes. Serum from patients with mild disease had significantly less suppressor activity. Lymphocytotoxic antibodies and suppressor activity were not correlated. Suppressor activity in immunoglobulin G fraction paralleled that found in whole serum. The present studies suggest that impaired delayed whole serum. The present studies suggest that impaired delayed hypersensitivity in SLE is a consequence of disease activity rather than an inherent feature of this disease. The strong correlation between serum suppression of PHA reactivity and anergy suggests that the humoral immunosuppressive effects described may be responsible, in part, for impaired delayed hypersensitivity in this disease.