Concerns about the toxicity of formalin dictate the need for alternative methods of tissue fixation. Alcohol-based fixatives have been proposed as optimal for immunohistochemical and nucleic acid methods and may be useful for diagnostic light microscopy. We recently converted our surgical pathology laboratory from 10% neutral buffered formalin to an alcoholic fixative (56% ethanol and 20% polyethylene glycol) and compared 100 consecutive cases after conversion with 100 formalin-fixed cases prior to conversion. One representative slide from each case was reviewed independently by four pathologists without knowledge of the fixative employed. The quality of fixation of each case was graded (0, very poor; 1, below average; 2, average; and 3, above average) based on the subjective composite evaluation of seven morphological features: tissue architecture, cell borders, cytoplasm, nuclear contours, chromatin texture, red blood cell membranes, and uniformity of staining. No significant difference in the quality of fixation was observed, although the average score of the alcoholic fixative was slightly lower than that of the formalin (2.59 vs 2.74). Interobserver concordance was 74%. Advantages of the alcoholic fixative included elimination of carcinogenic vapors, more rapid fixation, greater stain avidity, elimination of enzyme predigestion in immunohistochemical studies, and simple and rapid disposal. Disadvantages included slightly increased viscosity, increased variability of tissue staining and nuclear shrinkage, artifactual pigment deposition in bloody specimens, and increased flammability risk. Alcohol-polyethylene glycol appears to be a satisfactory alternative to formalin in routine diagnostic surgical pathology.