The absorption of some minerals has been shown to be affected by the presence of unhydrolyzed dietary triglycerides and free fatty acids generated from their partial hydrolysis. Since copper (Cu) can form poorly soluble soaps with long-chain fatty acids, we examined whether the uptake of Cu from the intestinal lumen is altered by the presence of fatty acids and triglycerides using an in vivo jejunal perfusion procedure. Long-chain fatty acids palmitate and stearate at 1.0 mM reduced Cu absorption rates compared with infusates without either fatty acid or triglycerides (means +/- SEM, controls: 104.4 +/- 8.8 pmole/min x cm vs palmitate: 12.5 +/- 17.6, P < 0.01; stearate:37.2 +/- 25.6, P < 0.05). Medium chain free fatty acids had no effect on Cu absorption (caprylate: 90.6 +/- 14.9, not significant; caproate: 69.5 +/- 14.2, not significant). Similarly, neither an emulsion of medium chain nor long-chain triglycerides at a total 1.0 or 2.5 mM concentration altered Cu absorption. The inhibitory effect of palmitate and stearate on Cu absorption was accompanied by a reduction in lumen-to-mucosa water influx (controls: 5.33 +/- 0.26 microl/min x cm vs palmitate: 3.20 +/- 0.70, P < 0.01; stearate: 3.36 +/- 0.52, P < 0.01). The data are consistent with a potential impairment of Cu intestinal absorption by long-chain free fatty acids which may accumulate in the jejunum following excessive fat intake and/or lipid malabsorption.