The yeast Pityrosporum orbiculare is one of the factors that may contribute to atopic dermatitis (AD). In the present study we compared the T-cell response to P. orbiculare in 12 AD patients with specific immunoglobulin (Ig)E antibodies (Ab) in serum against P. orbiculare with that of six non-atopic healthy controls. Freshly isolated peripheral blood mononuclear cells (PBMC) were cultured for 3 days in the presence of P. orbiculare extract. The proliferative response as measured by [3H]-thymidine incorporation was significantly higher in the AD patients than in the healthy controls (P < 0.05). Furthermore, significantly higher levels of interleukin (IL)-5 (P < 0.05), as analyzed by ELISA, were produced by PBMC from the AD patients compared to the healthy controls. Pityrosporum orbiculare-reactive T-cell lines (TCL) established by P. orbiculare stimulation of PBMC for 11 days produced significantly higher levels of IL-4 and IL-5 after stimulation with anti-CD3 Ab and showed a higher IL-4/interferon (IFN)-gamma ratio (P < 0.05) in the AD patients compared to the healthy controls. The higher proliferative PBMC response to P. orbiculare and the Th2-like cytokine production by P. orbiculare-stimulated TCL from AD patients indicate that P. orbiculare may play a role in maintaining skin inflammation in AD.