Guinea pigs multiply exposed to Xenopsylla cheopis adult fleas exhibited marked blood basophil responses to challenge infestation with only minor changes in blood eosinophil levels. Dermal responses to flea feeding were marked by dominant neutrophil (52% of the infiltrate) and eosinophil (32%) accumulations 24 hr after primary feeding, with a weak basophil response (11%). However, after challenge feeding 14 days later, eosinophils dominated, representing 59% of the infiltrate with basophils comprising 30% of the cellular response; neutrophils were rare (7%). Mast cells did not exhibit any increases in density during either the primary or secondary infestation, representing 4-7% of the infiltrate. These results demonstrate that flea feeding induces systemic and local basophil responses as demonstrated for all hematophagous arthropods examined so far. Flea feeding success was not adversely affected by feeding on homologously hypersensitized guinea pigs or guinea pigs sensitized by Ornithodoros parkeri feeding. However, basophil responses at flea feeding sites in heterologous (tick) sensitized animals were more basophilic (26 +/- 4 cells/0.03-mm2 area) than feeding sites in homologous (flea) sensitized hosts (9 +/- 6 cells). Furthermore, primary tick feeding sites become erythematous and indurated after flea feeding on the opposite flank, and were marked histologically by strong basophil abscess (276 +/- 56 cells/0.03-mm2 area); primary flea feeding sites were not activated by tick challenge feeding. These cross-generic challenge feeding experiments suggest antigen cross-reactivity, resulting in activation of feeding sites of a heterologous arthropod.(ABSTRACT TRUNCATED AT 250 WORDS)