This study documents the affinity of hematoporphyrin derivative (HpD) for human colorectal cancer by analysis of surface fluorescence. Ten patients undergoing elective surgery for primary colorectal cancer received intravenous HpD (2-5 mg/kg) either 3 or 72 hours preoperatively. Fluorescent photographs were taken of freshly resected specimens and analyzed using a computerized videodensitometric technique. This technique subtracted contaminating non-HpD fluorescence and facilitated estimation of HpD tissue levels. The HpD-specific fluorescence localized to tumors in all cases, and the mean HpD concentration was six-fold greater in malignant tissue than in surrounding normal mucosa (0.6 microgram/g versus 0.1 microgram/g, P less than 0.001). The authors conclude that HpD preferentially localizes to human colorectal cancer and this is relevant to the photodetection and phototherapy of colorectal neoplasia.