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Blood basophil responses were quantified in guinea pigs sensitized by infestation with larval Rhipicephalus appendiculatus (ixodid) and nymphal and adult Ornithodoros tartakovskyi (argasid) ticks, and in normal controls. In addition, blood eosinophil responses were examined in hosts infested with larval R. appendiculatus. Hosts exposed to primary and secondary infestations with R. appendiculatus exhibited similar elevations in blood basophils up to day 3 of infestation, when levels were increased fourfold over control (uninfested) hosts. By day 4, basophil levels in primary hosts were reduced markedly, whereas in secondary hosts they were still increasing and peaked at a level nearly twice that of primary hosts and seven times normals. Blood eosinophils did not respond to primary tick feeding but exhibited a marked diphasic response to secondary tick infestation, peaking on days 2 and 5. Animals exposed twice to R. appendiculatus ticks exhibited acquired resistance when challenged, resulting in 5% tick yield compared to 27% tick yield from primary hosts. Guinea pig blood basophil responses to primary and secondary nymphal and primary adult O. tartakovskyi feedings were greater in intensity and occurred earlier than in animals parasitized by R. appendiculatus ticks. This finding indicates a greater host sensitivity to O. tartakovskyi salivary secretions, substances crucial to the feeding process. Basophil levels in primary and secondary hosts peaked on day 2 or 3, then remained elevated in primary hosts and fell rapidly in secondary hosts. Adult challenge feedings resulted in anamnestic-type blood basophil responses that were evident by 6 hours and yielded greater maximum elevations (nine times normal) than nymphal hosts (five times normal). O. tartakovskyi-sensitized animals failed to express acquired resistance when challenged with O. tartakovskyi or R. appendiculatus. Furthermore, there was no resistance to O. tartakovskyi even when a tertiary feeding occurred at the height of blood basophilia from a secondary feeding. Since these ticks probably ingested immune blood that contained basophils, it is unlikely that ingestion of sensitized basophils results in deleterious effects to these ticks.