Epidermal Langerhans cells (ELC) are bone marrow-derived immune cells that are important in allergic contact dermatitis. We examined the influence of calcium transport inhibitors, lanthanum and diltiazem hydrochloride, on allergic contact dermatitis induced by 1-chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Systemic lanthanum at a dose of 0.08 mg/kg and topical lanthanum (50 microliters of 10% solution) were given 5 d before DNCB sensitization. Systemic diltiazem (30 mg/kg per dy) was given for 3 d during sensitization with DNCB. In all animals, challenge with topical DNCB to the ear skin was performed 5 d after sensitization and ear swelling was measured. Twenty four hours post-DNCB challenge, animals receiving systemic lanthanum demonstrated a 56% decrease in contact hypersensitivity (ear swelling) compared with non-lanthanum-treated animals (0.08 +/- 0.03 mm vs 0.18 mm +/- 0.02 mm, p less than 0.01). Topical lanthanum produced a 58% decrease in contact hypersensitivity (0.20 +/- 0.02 mm vs 0.41 +/- 0.03 mm, p less than 0.01). The DNCB-induced ear swelling also resolved more quickly in animals treated with lanthanum. Systemic diltiazem produced a 67% decrease in ear swelling (0.05 +/- 0.01 mm vs 0.15 +/- 0.02 mm, p less than 0.001). A decrease in epidermal Langerhans cell density of 13 to 14% was produced by systemic lanthanum, detected by both ATPase staining and Ia staining, respectively (p less than 0.05). Approximately 20% of the Langerhans cells were morphologically abnormal, having become "rounded," and lacking normal dendritic processes. From these results, we infer that calcium transport across the cell membrane of ELC may be important in the regulation of their function. Lanthanides and other calcium-channel blockers may be useful pharmacologic agents to probe these phenomena.