Previous work has shown that the cheC gene product of Escherichia coli plays a key role in regulating the direction of flagellar rotation during chemotactic responses. An attempt was made to identify other stimulus transduction elements that interact with the cheC component by examining cheC revertants for functional suppressors. Approximately two-thirds of the revertants studied appeared to be due to back mutation or to second-site mutations near or within the cheC structural gene. The remainder of the revertants carried suppressor mutations that mapped at the cheZ locus. Half of these suppressors impaired chemotaxis in a cheC+ background and were shown by complementation analysis to be defective in cheZ function. These suppressors corrected cheC defects in an allele-specific pattern, suggesting that the cheC and cheZ proteins are in direct contact and are mutually corrective due to protein-protein interaction. Observation of swimming patterns and flagellar rotation in cheC cheZ mutants demonstrated that the interaction of these two gene products influences both the spontaneous frequency of flagellar reversals and the ability of the rotational machinery to respond to chemotactic stimuli. A model of this interaction and its possible role in chemotaxis are discussed.