Hapten-specific and mast-cell-dependent biphasic (immediate and delayed-onset) cutaneous reactions were induced in a murine model by intravenous injection of anti-DNP IgE antibodies followed by a skin test. Four daily applications of topical 1 alpha,24(OH)2D3 ointment significantly inhibited both the immediate and the delayed-onset cutaneous reactions in a dose-dependent fashion, as well as the croton-oil-induced cutaneous reaction and DNFB contact sensitivity reaction. 1 alpha,24(OH)2D3 itself did not show any sensitizing or irritant potential. The inhibitory effect of 1 alpha,24(OH)2D3 on these reactions was limited to the application site and no systemic effect was observed. Another vitamin D3 analog 1 alpha,25(OH)2D3, also showed an inhibitory effect on IgE-mediated cutaneous reactions. These results suggest that topically applied 1 alpha,24(OH)2D3 might modulate IgE-mediated cutaneous reactions and could thus be useful in the treatment of certain human cutaneous disorders other than psoriasis and related keratinizing disorders.