The absorption and disposition of orally administered chloramphenicol palmitate (chloramphenicol-P) was studied in seven neonates (four preterm, three term). The highest measured chloramphenicol serum concentrations occurred greater than or equal to 4 hours after the dose, and ranged from 5.5 to 23 micrograms/ml after doses of chloramphenicol-P 50 mg/kg/day orally. The dosage had to be increased in all preterm neonates from 25 mg/kg/day to 50 mg/kg/day to obtain adequate serum levels during therapy. In four neonates the apparent half-life could not be estimated, because there was no decline in serum concentrations. The apparent half-life was 3 and 6 hours, respectively, in two neonates in whom the serum concentration declined during the dosing interval. Urinary excretion of chloramphenicol and the glucoronide ester in three neonates varied from 24% to 55% of the total dose administered. These preliminary data suggest considerable variability in serum chloramphenicol levels when chloramphenicol-P is administered orally in neonates. The delay in achieving the maximum serum concentration, nondeclining serum curve, and low renal recovery is indicative of incomplete, prolonged, and erratic absorption, possibly related to delayed gastric emptying or decreased intraluminal hydrolysis of the palmitate ester.