Expression levels of adhesion molecules on HMC-1 mast cells were examined prior to and following administration of 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. While most receptors (including ICAM-1) remained unchanged by the treatment, solely ICAM-3 expression was promoted in a dose- and time-dependent fashion, peaking at 50 nM of 1,25(OH)(2)D-3 and 72 h, illustrating that like other myeloid cells, human mast cells are 1,25(OH)(2)D-3 responsive, yet in a highly selective manner. Flow cytometric results were confirmed by ELISA, by semiquantitative RT-PCR, and functionally by showing enhanced anti-ICAM-3 mediated homotypic aggregation of 1,25(OH)(2)D-3 pretreated cells. Since cellular responsiveness is conferred by the vitamin D-3 receptor (VDR), we examined human mast cells for its expression. VDR was constitutively present in both HMC-1 and skin mast cells by RT-PCR technique and in nuclear extracts of HMC-1 cells by Western blot analysis. Our data thus suggest that human mast cells are direct targets of 1,25(OH)(2)D-3 action.