Waterfowl-origin influenza (WFOI) viruses were evaluated for their tissue tropism and replicative properties in chickens. The 14 WFOI isolates used in this study represented 13 different hemagglutinin-neuraminidase combinations recovered during 1987 and 1988 and included isolates possessing the H5 and H7 hemagglutinin subtypes and one isolate possessing the H5N2 combination. Following intravenous challenge, the frequencies of virus recovery within individual experiments were generally higher for the lower digestive tract and kidney samples. Virus titers ranged up to 10(8.5) mean embryo infective doses per gram of kidney tissue in clinically normal chickens. Differences in frequencies of virus recovery and virus titers in tissues indicated that some of these uniformly nonpathogenic and low-pathogenicity WFOI virus isolates replicated more extensively in chickens than did others. This enhanced ability to replicate in chickens should be further evaluated as a potential factor associated with the threat WFOI viruses present to poultry.