The objective of the present studies was to determine the effect of IL-6 on proliferation and FSH-induced estrogen production by granulosa cells from small (1-5 mm) and large (> or = 8 mm) bovine follicles. FSH-induced estradiol production by granulosa cells from large follicles (expressed as pg estradiol/10(5) cells/24 h) was not affected (p > 0.05) by 0.1, 1.0, or 10 ng/ml of interleukin (IL)-6, whereas 30 and 100 ng/ml of IL-6 inhibited (p < 0.05) FSH-induced estradiol production by 32% in cells from large follicles. In comparison, all doses of IL-6 inhibited (p < 0.05) FSH-induced estradiol production in cultures of cells from small follicles; maximal inhibition was achieved (75% decrease) with > or = 10 ng/ml. IL-6 was also a more potent inhibitor of cell proliferation in cultures of cells from small (55% inhibition) than from large (32% inhibition) follicles. In summary, IL-6 has a more potent inhibitory effect on proliferation and FSH-induced estradiol production by bovine granulosa cells collected from small follicles than from large follicles. Thus, it appears that less differentiated granulosa cells (small follicles) are more sensitive to IL-6 than are highly differentiated granulosa cells (large follicles).