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Interleukin-1β (IL-1β) and interleukin-1α (IL-1α) were shown to act as motility factors for the human breast carcinoma cell lines SK-BR-3 and ZR-75-1 in vitro. Both cytokines induced transition from the stationary to the motile phenotype (spreading). IL-1β stimulated translocation, shape change and random migration (chemokinesis) of SK-BR-3 cells as demonstrated by time-lapse video recordings and by a modified Boyden chamber assay. Interleukin-6 (1L-6) stimulated spreading of the SK-BR-3 cells; an additive effect with IL-1β on spreading and fast plasma membrane movements was evidenced. In the SK-BR-3 cell line, the signal transduction of IL-1β and IL-6 differed, since only the effect of IL-6 on spreading was sensitive to pertussis toxin. Both IL-1β and IL-6 required protein synthesis to stimulate spreading, since cycloheximide inhibited the effect of the cytokines. Induction of an autocrine loop of IL-6 in the SK-BR-3 cells by IL-1β was unlikely, since after stimulation with IL-1β, no induction of IL-6 activity was measured, nor was inhibition of stimulated spreading seen in the presence of an antiserum against IL-6. Addition of IL-8 or of an antiserum against IL-8 did not affect spreading. We concluded that IL-1 and IL-6 could act as motility factors for human breast carcinoma cells, in both an independent and an additive way. Human squamous cell carcinoma COLO-16 cells were found to secrete factors with similar effects on the SK-BR-3 and ZR-75-1 cells as the aforementioned cytokines. Although the presence of IL-1α and IL-6 activity in the COLO-16 conditioned medium was confirmed, a number of arguments were found to assume that still other factors beside these two cytokines were responsible for the motility-stimulating effect of the COLO-16 conditioned medium.