OBJECTIVE: To report four cases of fixed drug eruption induced by hydroxyzine hydrochloride (Otarex, Teva, Israel). CASE SUMMARY: Four children with restlessness who were treated with hydroxyzine hydrochloride developed fixed drug eruption of the penis. Drug discontinuation was followed by complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration inhibiting factor (MIF) assay with hydroxyzine hydrochloride was positive. DISCUSSION: The pathogenesis of fixed drug eruption and the role of macrophage MIF assay in diagnosis is discussed. CONCLUSIONS: A fixed drug eruption induced by hydroxyzine hydrochloride is possible, but is a rare phenomenon.