We have studied the production of and the response to interleukin-2 (IL-2) by blood T lymphocytes from 83 untreated patients with six connective tissue diseases, each patient with a healthy age/sex matched control. SLE patients had markedly decreased production of IL-2, both when elicited with phytohemagglutinin (PHA) and when promoted by autologous mixed lymphocyte reaction (AMLR). They also had decreased response to IL-2. Conversely, patients with scleroderma had normal production of IL-2 with both stimuli and their lymphocytes responded to IL-2 similarly to, or even better than, controls. Patients with mixed connective tissue disease had decreased production of IL-2 upon PHA stimulation but it was normal in AMLR systems. Response to IL-2 was moderately diminished. Patients with rheumatoid arthritis showed moderately decreased production of Il-2 with both stimuli but a normal response to Il-2. Patients with Sjögren's syndrome had similar, but less marked defects than those of SLE. Patients with dermato-polymyositis showed decreased production of IL-2 in AMLR but normal production of IL-2 in response to PHA as well as normal response to IL-2. The differences found between the various connective tissue diseases support the notion that the T cell dysregulation that results from or leads to "autoimmunity" in them is peculiar to each disease.