We compared the acute toxicity and initial accumulation of the piscicide TFM (3-trifluoromethyl-4-nitrophenol) in the freshwater unionacean mussels, Obliquaria reflexa and Fusconaia flava. Acute 48 h toxicity tests were conducted to determine the LC50 values for each species. The initial uptake clearances of TFM were measured by exposing the mussels to [14C]-TFM and counting the radioactivity in four organ tissues (foot, gill, mantle and viscera) over 48 h. TFM was about 2-fold more toxic to O. reflexa (LC50 1.80 mg l-1) than to F. flava (LC50 3.81 mg L-1) and the difference was not explained by accumulation patterns. The initial uptake clearance rates (0–6 h) for the whole body were similar between the species (11.2 ml g-1 h-2 in O. reflexa and 9.5 ml g-1 h-1 in F. flava). The accumulation of TFM residues among the organ tissues was also similar between species. The uptake clearance rates (ml g-1 h-1) of TFM equivalents were generally highest in the gill, but not significantly different than other organ tissues. The normalized concentration of TFM residues (μg per g whole body) was highest in the viscera. The toxicity data suggest that the mortality of both species would be minimal from sea lamprey control treatments with TFM. However, the behavioural effects and accumulation rates also indicate that mussels do not effectively avoid TFM exposure by valve closure.