A biological survey was conducted during August and September of 1964 of the Susquehanna River and its major tributaries, with bottom organisms selected as the primary indicator of biological water quality. Fish and algae were also given consideration when observed. Downstream from Northumberland, the river on both sides was found to be physiologically well suited to support many kinds of bottom dwelling organisms and did not exhibit any gross biological degradation. Localized impairment to biological quality was observed as a result of the deleterious effects of mine drainage, coal fines, and organic wastes contributed by certain tributaries. Unpolluted biological conditions in the impoundments downstream from Columbia, Pennsylvania, were indicated by known fishery studies; plankton data from above the dams at Holtwood, Pennsylvania, and Conowingo, Maryland; and additional data from the National Water Quality Network Station at Conowingo.