A 15-year-old boy experienced a macular serpentine erythematous eruption that subsided with a persistent hyperpigmentation overlying the superficial venous network of the left forearm. This reaction occurred at the injection site of a chemotherapy regimen that combined actinomycin and vincristine a few hours after the first course. After a single injection of actinomycin in the right arm, a similar reaction occurred, implicating it as the responsible agent. A skin biopsy specimen demonstrated a cell-poor interface tissue reaction associated with an eccrine neutrophilic hidradenitis. To our knowledge, this is the first case of persistent supravenous serpentine hyperpigmented eruption reported in a child treated with this particular drug combination. (J Am Acad Dermatol 2000;43:540–6.)