Osmotic fragility was examined in red blood cells taken from miniature poodles with progressive retinal atrophy (PRA). In this study, the median osmotic fragility for erythrocytes (concentration of NaCl required for 50% haemolysis) was found to be significantly lower for clinically affected, compared to unaffected animals. These differences were maintained regardless of changes in erythrocyte incubation pH (7.0, 7.5). There was no difference in the slope parameter of erythrocyte osmotic fragility profiles for both sets of animals, indicating a similar variability of erythrocyte age. In groups of animals maintained with the same diet and fasted for 12 hr, and in groups of animals with no dietary constraints, total plasma cholesterol was significantly lower for affected, compared to unaffected animals. Red blood cell indices were also assessed; mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), red blood cell count (RBC) and blood haemoglobin concentration (Hb) were normal, while erythrocyte packed cell volume (PCV) was significantly reduced for affected, compared to unaffected. Data from this study suggest that the abnormal erythrocyte osmotic fragility of affected animals is unlikely to be a consequence of a higher erythrocyte surface area/volume ratio, higher plasma cholesterol concentration, or greater proportion of new to old erythrocytes, and that a general membrane defect might be associated with prcd in the miniature poodle.