Factors influencing diagnostic yield by directed endoscopic biopsy and cytology were studied in 50 patients with advanced gastric cancer using a forward-viewing panendoscope. The diagnostic yield was higher for exophytic lesions than for infiltrative tumor, and directed brush cytology alone was more productive than directed biopsy alone. The lesions that provided non-diagnostic tissue were mostly recurrent or infiltrative cancers, and were most often in the cardia, antrum, or were of the linitis plastica type. The combination of infiltrative character and location in antrum or cardia, especially if recurrent, often resulted in non-diagnostic biopsy and cytology specimens.