Little is known about the ontogeny of cyclooxygenase activity and synthesis of prostaglandins in the developing gastrointestinal tract. We tested the hypothesis that an age-related increase in cyclooxygenase as reflected in production of PGE2 in the proximal small bowel (PSB) is associated with the maturation of the mucosal barrier as determined by 51Cr-EDTA permeability. Cyclooxygenase activity in PSB of rats at 10, 22, 36, and 63 (adult) days of age was determined by the generation of PGE2 using specific radioimmunoassay. Systemic 51Cr-EDTA clearance into the lumen was used to assess mucosal barrier function in PSB in 10- to 12-day-old and adult rats. Prostaglandin E2 generation rose significantly from 24.8 +/- 0.4 pg/mg/min in 10-day-old rats to 125.0 +/- 7.8 in adult rats. The 51Cr-EDTA clearance decreased significantly from 5.08 +/- 0.90 ml/min/100 g in 10- to 12-day-old rats to 0.43 +/- 0.18 ml/min/100 g in adult rats. To assess the possible role of endogenous PGE2 in directly mediating these observed changes in the mucosal permeability, a group of adult rats chronically received indomethacin (2.5 mg/kg/day) over a 3-day period, while another group of vehicle-treated rats served as controls. The 51Cr-EDTA clearance of the indomethacin-treated rats was significantly higher than the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)