Steroids are frequently used to treat inflammatory conditions in which lymphocytes play a role. We have recently shown that in severe ulcerative colitis, treatment outcome correlates better with in vitro estimates of lymphocyte steroid sensitivity (LSS) than with disease severity. This lead us to examine the range and variability of LSS in the healthy population. Dexamethasone inhibition of lymphocyte proliferation was measured on 54 occasions in 18 volunteers (mean age, 46 yr; range, 23-60 yr) over an 8-month period. Inter- and intra-assay variation in LSS was low when expressed as maximum inhibition achieved, Imax (2.9% and 3.4%, respectively), allowing us to demonstrate a very wide variation in Imax between healthy individuals (-6.7% to 99.7%). In contrast, within-individual variation of Imax was significantly less than between-individual variation (F test, P < 0.0001), consistent with stability of this parameter over time. No correlation was seen between LSS and glucocorticoid receptor density or affinity, suggesting a postreceptor mechanism. Serum cortisol at the time of sampling and skin sensitivity to glucocorticoids also failed to correlate with LSS. This study suggests Imax is a sufficiently stable parameter to categorize healthy individuals according to LSS. The wide range of LSS demonstrated is striking and suggests that up to 30% of the healthy population would fail to respond to steroid therapy for severe inflammatory conditions.