Viscum album agglutinin (VAA) is an extract component of mistletoe. It belongs to the plant lectin family and exerts various biological effects such as cytotoxic properties for tumor cells in culture. VAA as well as galectin-1, an endogenous lectin, possess galactose-specific surface-binding sites. We therefore investigated 159 cases of lung cancer for their capacity to bind VAA and galectin-1 and for Lewis antigen reactivity. Three different methods were used for detection of VAA: a two-step method with biotinylated VAA; an immune complex three-step method, and a four-step method. The most sensitive results were obtained with the four-step method utilising VAA, a goat-anti-VAA antibody and a biotinylated rabbit-anti-goat antibody. Intensity and distribution of staining were assessed using an immunoreactive score index (0-12). Approximately 70% of all tumors exhibited moderate to strong binding capacity for VAA. Adenocarcinomas and bronchiolo-alveolar carcinomas were more frequently labeled than squamous carcinomas. No relationship between expression of binding sites for VAA and galectin-1 as well as of Lewis antigens was found. Moreover, there was no correlation between VAA-binding capacity and survival, whereas expression of galectin-1-binding sites was of prognostic significance. Patients showing expression of galectin-1-binding sites revealed a better prognosis than those lacking binding sites or showing a weak reactivity (P = 0.0257 log rank test of Kaplan-Meier statistics).