In this study, we investigated whether an interleukin 2 (IL-2) secretion defect by peripheral blood mononuclear cells (PBMCs) after in vitro stimulation with phytohemagglutinin (PHA-M) occurs in either newly diagnosed or long-standing type I (insulin-dependent) diabetic patients and whether it is accompanied by a dysregulation of soluble IL-2-receptor (IL-2RS) production. PBMC cultures (2.5 x 10(6) cells), unstimulated or stimulated with PHA-M (25 micrograms/ml), from 20 type I diabetic patients (10 with time since onset less than 3 mo and 10 with long-term diabetes of less than 3 yr) and 10 control subjects were studied for the production of IL-2 and IL-2RS in their respective supernatants. No difference was found in IL-2 production in unstimulated cultures of type I patients compared with control subjects, although a significant decrease from PHA-M-stimulated cultures were seen (newly diagnosed, 1.7 +/- 0.3 ng/2.5 x 10(6) cells; long-standing, 2.2 +/- 0.3 ng/2.5 x 10(6) cells; P less than .001 and P less than .05, respectively) compared with control subjects (3.6 +/- 0.4 ng/2.5 x 10(6) cells). In regard to the production of IL-2RS, no difference exists for unstimulated cultures, whereas, after PHA-M stimulation, both newly diagnosed and long-term-diabetic patients showed a decrease in the IL-2RS levels (318 +/- 50 and 331 +/- 62 U/2.5 x 10(6) cells; P less than .02 and P less than .05, respectively) compared with normal subjects (463 +/- 34.2 U/2.5 x 10(6) cells). Thymus-activated cell phenotypes confirmed the T-lymphocyte activation after a 48-h culture period.(ABSTRACT TRUNCATED AT 250 WORDS)