The role of nasal-associated lymphoid tissue (NALT) as a mucosal inductive site for tear IgA antibody responses was investigated in the rat model. Fluorescent microspheres were shown to access and be taken up by NALT after intranasal of ocular-topical administration, although fewer microspheres were found in the latter case. Tear IgA anti-DNP antibody responses to dinitrophenylated Streptococcus pneumoniae were 6 micrograms/ml at day 7, 10 micrograms/ml at day 10, and were still detectable on day 21 (5 micrograms/ml) following ocular or gastrointestinal immunization. Intranasal immunization induced tear IgA responses which were 1.7-fold higher at day 7 (10 micrograms/ml), peaked by day 10 (14 micrograms/ml) and were still 1.6-fold higher (8 micrograms/ml) at day 21 than responses of ocular or gastrointestinal groups. These findings suggest that intranasal immunization may be more effective than ocular or gastrointestinal administration in eliciting tear IgA antibody responses and, taken together with the microsphere data, indicate that NALT can serve as an inductive site for ocular mucosal IgA responses.