In guinea pigs, macroscopic cutaneous reactions to initial (primary) Ixodes holocyclus feeding were first apparent at 96 hr post-tick attachment, peaked at 7 days (5 mm), and were gone by Day 14. Microscopic analyses of these primary tick feeding sites at 12, 24, 48, 72, and 96 hr post-attachment revealed the dominance mononuclear cells (63-94% of the infiltrate) at all times. Neutrophil levels were high initially (34% of the infiltrate), but quickly subsided to 6-15% of the cellular response. Eosinophils were essentially absent from primary sites, comprising only 1-3% of the infiltrate. Basophils were absent initially, but accumulated in small but significant numbers (12% of the infiltrate) at the epidermal-dermal border by 96 hr post-tick attachment, 3 days prior to maximum erythematous skin reactions. In sensitized and challenged (secondary) animals, erythematous reactions in response to secondary tick feeding were apparent as early as 18 hr post-tick attachment with peak responses at 48 hr (3-4 mm). Cutaneous leukocyte responses to challenge feedings were quantitated at 12, 24, 48, and 72 hr post-tick attachment and consisted initially (12-24 hr) of a strong mononuclear cell response (72-79% of the infiltrate) that was replaced by a dominant basophil response at 48 and 72 hr. Strong cutaneous basophil responses coincided with a significant level of tick rejection. Eosinophils and neutrophils were virtually absent from these secondary responses.(ABSTRACT TRUNCATED AT 250 WORDS)