As a persistent bioaccumulative compound, perfluorooctanoic acid (PFOA) is found in various ecosystems and receives growing attention. The acute toxicity of PFOA was tested on 2 freshwater microalgae, Chlamydomonas reinhardtii and Scenedesmus obliquus. The 96-h concentration for 50% of maximal effect (EC50) values were measured, physiological responses of the algae were investigated, and uptake of PFOA by the algae was quantified. The EC50 values for C. reinhardtii and S. obliquus were 51.9 ± 1.0 mg/L and 44.0 ± 1.5 mg/L PFOA, respectively. After 8-d exposure to PFOA ranging from 10 mg/L to 40 mg/L, the growth of C. reinhardtii was significantly inhibited, whereas that of S. obliquus was only slightly suppressed. Increases in malonaldehyde and proline levels were observed in the 2 algae when exposed to PFOA at certain concentrations, for instance, 20 mg/L and 40 mg/L, which is indicative of the trigger of a defensive mechanism. The percentage of PFOA that was adsorbed by the algae after 8-d exposure at a dosage between 5 mg/L and 20 mg/L ranged from 5.5% to 7.5%, and the uptake of PFOA by the algae exceeded 10%.