The recent development of a sensitive two-site monoclonal antibody immunoassay for the major cat allergen (Fel d I) has made it possible to make accurate measurements of airborne cat allergen using low volume samplers that do not disturb the room. Houses with cats had from 2 to 20 ng Fel d I/m3 air compared with less than 0.2 ng/m3 in houses without cats. Using a cascade impactor and a multistage liquid impinger, the particle size distribution of airborne Fel d I in nine houses was 75% on particle greater than or equal to 5 microns in diameter and 25% (range, 10 to 62%) on particles less than or equal to 2.5 microns. In a cat vivarium with 12 cats, the air contained 40 ng Fel d I/m3, but less than 2% was detected on particles less than or equal to 2.5 microns. The air exchange rate in the vivarium (approximately 15 changes/h) appears to be the major difference from domestic houses (less than 0.5 changes/h). Repeated studies in one house confirmed a very high proportion (approximately 60%) of Fel d I on small particles. During domestic cleaning, the levels of small particle allergen in this house approached those produced by a nebulizer for bronchial provocation, i.e., 40 ng/m3. These results show unequivocally that significant airborne Fel d I is associated with small particles, which remain airborne for long periods. These findings are strikingly different from previous results obtained with airborne dust mite allergen. The results provide an explanation for the distinctive rapid onset of asthma or rhinitis in patients allergic to cats and a basis for designing a policy to reduce airborne allergen in houses with cats.