Deficient production of nitric oxide may be responsible for the defective defense barrier and persistence of bacterial infection. To gain insight into amino acid-metabolism and L-arginine-nitric oxide system, we studied 34 end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) (20 males, 14 females, with a mean age of 53.5 years and a mean duration on PD of 29.7 months). The concentrations of amino acids, including L-arginine, were measured in peritoneal dialysate and in the serum. The data demonstrated that patients with ESRD on PD have normal serum amino-acid profiles, whereas those with acute peritonitis develop L-arginine deficiency (from 99 +/- 9 to 52 +/- 9 mumol/L). In addition, levels of asparagine, glycine, proline (nonessential) as well as valine, threonine, and lysine (essential) were reduced in patients with peritonitis. The majority of patients with acute bacterial peritonitis have increased nitric oxide production as judged by the level of nitrites in the dialysate (36 +/- 2 vs 57 +/- 6 mumol/L). The recovery from peritonitis was associated with a decline in nitric-oxide generation. There was a smaller subgroup of these patients that showed paradoxically low nitrite levels during acute peritonitis. The nitrite: L-arginine ratio in the peritoneal dialysate was increased in patients with peritonitis, further suggesting the development of substrate deficiency. These findings implicate L-arginine as a conditionally essential amino acid in PD patients with acute peritonitis. Further studies are needed to address the issue of L-arginine supplementation in such patients.