1. This study examined the influence of H 2 O 2 , interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H 2 O 2 (10 −8 -10 −4 mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [ 3 H]thymidine incorporation and cell counts. 2. Although one pulse of H 2 O 2 had no significant effect on mesangial cell proliferation, three daily pulses of 10 −6 mol/l H 2 O 2 resulted in a significant increase in [ 3 H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) ( P <0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [ 3 H]thymidine incorporation increasing by 19 (36.7, −6.7)% ( P <0.05) and 53.5 (107, 21.9)% ( P <0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10 −6 mol/l H 2 O 2 [49.9 (77.7, 12.3)%] ( P <0.01), whereas the addition of 10 −6 mol/l H 2 O 2 to platelet-derived growth factor resulted in a summated increase in [ 3 H]thymidine incorporation of 82.7 (113, 57.4)% ( P <0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H 2 O 2 plus platelet-derived growth factor by 55.4 (77.7, 103)% ( P <0.05). 3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.