Patients exposed to the toxic dinoflagellate Pfiesteria develop an illness characterized by secretory diarrhea, conjunctival irritation, skin lesions, and varying degrees of neurologic manifestations. The anion-exchange resin, cholestyramine has been reported in one small case series to be an effective treatment of severe diarrhea associated with Pfiesteria intoxication. A 54-year-old man traveled to the Dominican Republic where he went swimming in what he describes as “dirty ocean water”. Within an hour, he noted a generalized burning and itching of his skin. Later on, he noted pruritic vesicular skin lesions, intense frontal headache, and conjunctivitis. A few days later, he complained of abdominal cramping, nausea, and hourly episodes of watery, nonbloody diarrhea. Due to the constellation of symptoms, Pfiesteria intoxication was suspected. On arrival in the United States, he sought medical care for continued symptoms. Physical examination was remarkable for conjunctival injection, linear vesicular lesions (5 cm in length) over his right ankle and left orbit as well as erythema over foreskin of his penis. Mental status and memory were normal. Laboratory studies revealed an elevated serum creatinine, which eventually normalized, and stool studies were negative for leukocytes, blood, and enteric pathogens. Intense diarrhea persisted until he was started on cholestyramine (4 g PO tid). The diarrhea resolved within 2 hours of starting treatment. The headache was initially treated with narcotic agents but only resolved with IV diphenhydramine (25 mg q 4 h). Cholestyramine and diphenhydramine appear to be effective therapeutic agents for tropical-related diarrhea and headache, respectively.