Pityrosporum yeasts have been implicated as a trigger for the initiation of scalp lesions in psoriasis. To determine whether Pityrosporum-reactive T cells are present in lesional psoriatic skin. T-cell lines (TCL) were cultured from the scalps of nine patients with psoriasis and seven with alopecia areata (disease controls), and from non-scalp lesions from six of the psoriatic patients. The psoriatic skin TCL were stained for CD3, CD4, CD8 and TCR alpha beta expression and tested in a proliferation assay with Candida albicans and purified protein derivative (PPD), and cytoplasmic and cell-wall extracts of P. ovale (oval) and P. orbiculare (round). The proliferative responses of corresponding peripheral blood mononuclear cells (PBMC) were also determined. All the PBMC samples responded to the Pityrosporum extracts to variable extents, but no significant difference in the response of the group to the two different forms of yeast was observed. The response was mediated by CD4+ T cells and inhibited by the addition of anti-HLA-DR antibody. In addition, all nine psoriatic scalp TCL, which were predominantly CD3+, CD4+ TCR alpha beta(+), responded to the cytoplasmic, and five of nine TCL to the cell-wall extract of P. orbiculare. In contrast, only three of the nine TCL proliferated to either extract of P. ovale. This difference was significant for both the cytoplasmic (P < 0.01) and cell wall (P = 0.01) extracts. Similarly, the TCL cultured from non-scalp psoriatic lesions also showed a more marked response to the P. orbiculare extracts (P = 0.05). Furthermore, four of seven and two of seven scalp TCL from lesions of alopecia areata responded to the P. orbiculare and P. ovale extracts, respectively; these responses did not differ significantly from those of the psoriatic scalp TCL. None of the skin TCL responded to either Candida albicans or PPD. These findings demonstrate that T cells with differential reactivity to the round and oval forms of Pityrosporum are present in, but are not specific for, psoriatic skin lesions. A role for these cells in the pathogenesis of psoriasis remains speculative.