The usefulness of a test for slime production as a marker for clinically significant infections with coagulase-negative staphylococci and its implications for therapy were examined. Hospital records were reviewed for 59 patients from each of whom more than one isolate of coagulase-negative staphylococci was obtained. In patients with a prosthetic device, 81% of 59 infectious episodes were due to a slime-positive coagulase-negative staphylococci. In contrast, 22 noninfectious episodes (in which the organisms were contaminants) were equally distributed between episodes due to slime-positive or slime-negative isolates (P = .005). Only 32% of infections caused by slime-positive organisms, in contrast to 100% of infections caused by slime-negative organisms, were improved by treatment with antibiotics alone (P = .02). Prosthetic device removal in addition to antibiotic treatment significantly improved the outcome in patients with infections due to slime-positive organisms when compared with treatment with antibiotics alone (93% vs. 32% improvement; P = .00025).