Mucocutaneous cultures obtained at admission and subsequent weekly nasopharyngeal cultures were obtained on 182 infants in the neonatal intensive care unit (NICU) over 3 months to assess whether a relationship existed between colonization with coagulase-negative staphylococci and invasive infection, particularly with respect to slime production. Nasopharyngeal colonization by coagulase-negative staphylococci occurred in a mean of 58% of infants weekly, with an equal prevalence of slime-positive and slime-negative isolates over time. Colonization of the nasopharynx on admission increased from 8.9% of those admitted within the first day of life to 33% of those admitted thereafter (p less than 0.005). The presence of slime-positive coagulase-negative staphylococci on admission was not predictive of later patterns of colonization with respect to slime. Of infants not colonized on admission who had subsequent cultures, 72% became colonized with coagulase-negative staphylococci that were equally likely to be slime-positive or slime-negative. The incidence of invasive infections was 4.4%. Infants with slime-positive mucocutaneous colonization were more likely to develop invasive coagulase-negative staphylococci disease than infants with slime-negative or no colonization (8.4% versus 1.1%; p less than 0.025). The incidence of slime-positive coagulase-negative staphylococci isolates from blood cultures was 6/7 (86%) whereas those from mucocutaneous cultures was 131/260 (50%) (p = 0.06). Colonization with slime-positive coagulase-negative staphylococci is a significant risk factor for developing invasive coagulase-negative staphylococci disease and these organisms are responsible for the majority of coagulase-negative staphylococci invasive infections.