The effect of peritoneal dialysate on the capacity of peripheral blood polymorphonuclear (PMNL) and mononuclear leukocytes (MNC) to release leukotriene B4 (LTB4) and tumor necrosis factor alpha (TNFα) was investigated in vitro. Following density gradient separation, aliquots of 5 × 106 PMNL or MNC were incubated in peritoneal dialysis fluid containing 1.5% glucose or Hanks’ buffer ( = control) for 1–2 h at 37°C. TNFα and LTB4 production was stimulated with Escherichia coli lipopolysaccharide (LPS) and calcium ionophore A23187, respectively. MNC incubated in buffer and LPS produced (mean ± SD) 1,006 ± 522 pg TNFα/5 × 106 cells; no significant amounts of TNFα were detectable in the presence of dialysate. An inhibition of TNFα release was also observed in MNC exposed to bicarbonate-buffered dialysates (pH 7.40) and 4.25% and 1.5% glucose solution with physiologic osmolality. Incubation of PMNL in Hanks’ buffer followed by A23187 stimulation led to production of 29.1 ± 19.2 ng LTB4/5 × 106 cells, whereas glucose-incubated cells were refractory to ionophore stimulation ( < 0.l ng LTB4/5 × 106 cells). The failure of dialysate-exposed leukocytes to release inflammatory mediators in response to adequate stimuli may contribute to the impairment of cellular host defense in the setting of continuous ambulatory peritoneal dialysis.