Our objective was to measure the relative proportions of messenger RNAs coding for soluble and membrane-bound Fas in peripheral blood mononuclear cells (PBMCs) and to quantify lymphocyte apoptosis in vitro in systemic lupus erythematosus (SLE). A RT-PCR (soluble/membrane Fas mRNA) ratio was calculated in 16 SLE, 11 RA and 16 healthy subjects' PBMCs. Apoptosis was quantitated in vitro using nick-end labeling and flow-cytometry analysis immediately and after overnight T cell activation. The mean soluble/membrane Fas ratio was 1.219+/-0.424 in the SLE group, significantly higher than in healthy subjects, 0.516+/-0.180 (P = 0.0001). There was no significant difference between inactive and active SLE groups whereas Fas ratio was higher in SLE patients with nephritis (1.460+/-0.365) compared to those without nephritis (1.031+/-0.380) (P=0.039). Mean soluble/ membrane Fas ratio in RA patients (0.975 +/- 0.37) was higher than in healthy subjects (P = 0.0003) and lower than lupus nephritis patients (P=0.015). A significantly higher proportion of mononuclear cells engaged apoptosis after T cell activation in active lupus patients, compared to control subjects. In comparison with healthy subjects, Fas alternative splicing was skewed toward the soluble form of Fas in SLE and RA. Apoptosis after T cell activation in vitro was increased in active SLE patients.