OBJECTIVES: The aim of this study was to perform a case-control medical evaluation of cats from multi-cat households presenting with inappropriate latrining and spraying behavior. METHODS: Owners of 18 'spraying' and 23 'latrining' cats with normal control subjects available from the same households were recruited for a case-control study. Otherwise overtly healthy dyads (each dyad consisting of a case cat and a control cat) were brought together to the veterinary hospital of the University of São Paulo for a medical work-up (ie, physical examination, complete blood count, biochemical profile, urinalysis and urine culture, abdominal ultrasound of the urinary system and in females, where possible, cystoscopy). RESULTS: Medical problems were identified with similar frequency in the 'sprayers' (38.9%), 'latriners' (39.1%) and controls of the latrining group (26.1%), but not the controls of the spraying group (5.5%). The difference between 'cases' and 'controls' from spraying households was significant. Common potential health-related changes include renal insufficiency, cystitis and bladder lithiasis. Renal calculi, higher creatinine levels (within normal reference interval) and 'glomerulations' (detected during cystoscopy) were also found in the remaining sprayers and latriners that were considered clinically healthy. Post-cystoscopy, a new form of periuria occurred in two cats (one sprayer and one latriner). CONCLUSIONS AND RELEVANCE: These results indicate that spraying or latrining behavior in the home, as well as living with a cat that is not using the litter box as a latrine, are all associated with a higher level of urinary tract abnormalities; living with a cat that is spraying, however, does not have this association. The findings also suggest that both forms of periuria might be associated with interstitial cystitis. We therefore conclude that all cats with periuria need to be carefully evaluated medically and that treatment of latrine-related problems should consider all cats in the house, whereas spraying may be more focused on the individual displaying the problem.