BACKGROUND: Adipokines are a group of fat-secreted hormones and cytokines, including leptin and adiponectin, with important functions in humans. Peritoneal dialysis (PD) is associated with markedly raised plasma adipokines, suggesting increased production in this setting. We have shown that low pH down-regulates leptin production. The current study was designed to test if novel pH-neutral PD fluids may regulate leptin and adiponectin secretion in vitro. METHODS: We exposed 3T3-L1 adipocytes to a 50 : 50 mixture of dialysate and M199 containing 10% serum for upto 48 h. Dialysates were commercial PD fluids, i.e. conventional acidic, lactate-buffered solutions (PD-acid) and pH-neutral lactate-buffered (PD-Bal) or bicarbonate-buffered solutions (PD-Bic). Leptin and adiponectin concentrations in culture-cell media were measured by ELISA. RESULTS: Compared with PD-acid, PD-Bal and PD-Bic produced a 25 and 43% increase, respectively, in leptin secretion at 48 h (P < 0.05). In contrast, adiponectin secretion was not affected. High glucose PD fluids (4.25%) specifically inhibited leptin secretion vs 1.5% glucose, buffer-matched solutions (P < 0.05). However, differences in leptin secretion due to pH and type of buffer remained significant. In further experiments, the pH of test media were extensively varied without the presence of dialysates. Leptin secretion was shown to increase in a parallel to pH, whereas large changes in pH did not affect adiponectin secretion. CONCLUSION: The pH-neutral PD solutions specifically induce leptin, but not adiponectin secretion from 3T3-L1 adipocytes. PD-Bic produced a greater leptin stimulation than PD-Bal, but this difference was attributable to pH per se, rather than the type of buffer.