The various histopathologic alterations detected in the liver of the frog Rana ridibunda from a small river of Northern Greece were investigated. In the livers of the frogs collected from this river, there was an increase in the area occupied by melanomacrophages as well as an increase in their color intensity. Mild karyomegaly and polyploidy, together with solitary and focal accumulation of infiltrates (neutrophils and lymphocytes), was evident. Three different kinds of foci were detected basophilic focus, vacuolated focus, and a special type of focus with nodules surrounded by collagen. Some bile ducts were found to be filled with periodic acid schiff (PAS)-positive amorphous material mixed with cellular debris. In liver foci of dense connective tissue, with structures resembling bile ductuli, were detected. The latter finding supports the conclusion that this might be early holangiofibroma. Progressive fibrosis around bile ducts, which extended into the hepatic parenchyma, was obvious. Given that the river under study was previously characterized as being moderately to heavily polluted, it was concluded that a number of environmental factors, including heavy metals, might be responsible for these histopathologic alterations.