The growth responses of six human pancreatic cancer cell lines (SW-1990, PANC-1, MIA PaCa-2, BxPC-3, RWP-2 and CAPAN-2) to cholecystokinin (CCK) were evaluated in serum-free medium (SFM). In each experiment cells were initially plated in media containing fetal calf serum (FCS) grown for 48-72 h, and then washed with saline. Cells were incubated for an additional 72 to 96 h in medium devoid of FCS in the absence (control) or presence of synthetic CCK analogue (Thr4,Nle7)CCK9 (10(-13) to 10(-9) M), or CCK8 (10(-12) to 10(-9) M), or CCK39 (10(-12) to 10(-9) M). Viable cell counts were performed with a hemocytometer. Growth of each cell line was stimulated in the presence of CCK in serum-free medium, although the magnitude of responses differed. The concentrations of (Thr4,Nle7)CCK9 which stimulated the greatest increase in cell counts as compared to controls for each cell line were: SW-1990, 39% (10(-12) M, P less than 0.05); PANC-1, 45% (10(-9) M, P less than 0.005); MIA PaCa-2, 42% (10(-12) M, P less than 0.005); BxPC-3, 32% (10(-13) M, P less than 0.05); RWP-2, 37% (10(-11) M, P less than 0.005). Maximal response to CCK8 occurred at the 10(-9) M dose for each cell line: MIA PaCa-2, 40% (P less than 0.025); PANC-1, 85% (P less than 0.001); RWP-2, 68% (P less than 0.001) and CAPAN-2, 52% (P less than 0.001). The maximal increase in cell count with CCK39 ranged from 44-74% and occurred with either 10(-11) or 10(-10) M. CCK8 in SFM also stimulated cell growth as well as or better than FCS alone in three out of four pancreatic cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)