The results of clinical, laboratory and therapeutic observations conducted over a seven year period in 40 expatriates from the tropics who presented in New York City with overt tropical sprue have been described. The majority of subjects presented with symptoms referable to the gastrointestinal tract, weight loss and weakness. Only nine were symptomatic at the time of arrival; the remainder developed symptoms within several months to 14 years after arrival. Thirty-five subjects had a megaloblastic anemia; this was a secondary to a combined deficiency of folate and vitamin B12 in 25 and to deficiency of only one of these vitamins in the other ten. Serum concentrations of albumin, calcium, and cholesterol were subnormal in approximately one-half and the serum carotene concentrations were low in all but two subjects. Serum values of one or more immunoglobulin were reduced in 19. All 40 subjects had malabsorption of xylose; 12 of 19 tested had malabsorption of a pharmacologic dose of folic acid; 27 of 28 tested had malabsorption of vitamin B12; and 23 of 27 persons tested had steatorrhea. Jejunal morphology was abnormal in 34 of 35 subjects biopsied prior to treatment; villi were completely absent in four and showed changes of moderate severity in 30. Treatment with pharmacologic doses of folic acid or vitamin B12 produced a clinical remission in 18 of 21 patients. This remission was sustained in all 14 subjects who were followed for periods of from one to four years and reevaluation of intestinal morphology and function in nine showed improvement in all, but return to normal in less than one-half. Treatment with oral tetracycline for three weeks resulted in clinical improvement in 11 of 12 subjects, a hematologic response in nine of the ten cases who had a megaloblastic anemia, increased absorption of xylose and cessation of steatorrhea in all, and improved jejunal morphology in 11. Vitamin B12 absorption remained subnormal in nine. Continued antibiotic therapy for six months in eight patients was associated with additional weight gain, further improvement in jejunal morphology and xylose absorption in all, and return of vitamin B12 absorption to normal in all except one. Fifty asymptomatic expatriates from the West Indies were surveyed for abnormalities of intestinal function. The absorption of xylose was reduced in six (24%) of 25 subjects who had been resident in a temperate climate for less than one year but in only one (4%) of 25 persons who had been away from the tropics for more than a year.(ABSTRACT TRUNCATED AT 400 WORDS)