The acute intraperitoneal LD50 values of hydroxynonachlorodiphenyl ethers (HO‐Cl9‐DPEs) in mice have been determined. The acute toxicity of each of these compounds is compared with that of pentachlorophenol (PCP) and 2‐hydroxy‐2’,4,4'‐trichloro‐diphenyl ether (2‐HO‐Cl3‐DPE; Irgasan DP‐300; Triclosan), a commonly used bactericide. The order of acute toxicity observed was: 2‐HO‐Cl9‐DPE > technical PCP ≈ pure PCP > 3‐HO‐Cl9‐DPE > 4‐HO‐O,‐DPE > 2‐HO‐Cl3‐DPE. Symptomatology following exposure to the HO‐Cl9‐DPEs was similar to that observed for PCP, a known uncoupler of oxidative phosphorylation. 2‐HO‐Cl3‐DPE, however, produced clinical signs suggestive of a suppressive effect on the central nervous system. Data on time response following a lethal dose of each of these compounds was also obtained.