We studied etiologic factors important in colonization of 179 central venous catheters (CVCs) in patients randomized into group 1 (who received daily topical applications of povidone-iodine) or group 2 (who received only dry dressing changes). Colonization rates of CVC tips were similar between group 1 (18/84 or 21%) and group 2 (22/95 or 23%). Peripheral blood cultures grew Candida in eight hyperalimented patients (evenly divided between groups 1 and 2), S epidermidis in four other patients (also evenly divided), and gram-negative bacteria in three patients. Colonization rates for CVCs in place for 0 to seven days was 15.6% (17/109) and 76.7% (23/30) if used from eight to 30 days. Inflammatory signs at CVC sites were often absent when CVCs became colonized or produced bacteremia. Unimportant determinants of CVC colonization included skin securement of CVCs, antibiotic infusions through CVC lines, and masking and gowning of physicians before CVC placement. Daily applications of povidone-iodine did not reduce colonization of CVCs as compared to dry dressing changes.