Outbred OF1 mice were immunized subcutaneously with flu vaccine, either in the neck or in the lumbar region (back), in combination with adjuvants inducing either a Th1- or a Th2-type response, referred to as adjuvants A1 and A2, respectively. After two parenteral immunizations, the mice were boosted intranasally with nonadjuvanted vaccine. The serum response was analyzed after each immunization by measuring specific immunoglobulin A (IgA), IgG1, and IgG2a antibody levels, while the local response (same isotypes) was measured in the salivary glands after the mucosal boost by ELISPOTs. We observed that systemic priming at any of the two sites with a Th2 rather than a Th1 adjuvant dramatically enhanced the mucosal IgG1 and IgA responses following a mucosal boost with unadjuvanted vaccine. In addition, as judged by the IgG2a/IgG1 ratios and serum IgA levels, immunization of mice in the back induced a rise in Th2 response compared to neck immunization with adjuvant A1. In contrast, such back immunization with adjuvant A2 reversed the Th1-Th2 balance in favor of the Th1 response compared to neck immunization. Similar differences were observed in mucosal antibody levels according to the site of priming with one given adjuvant; priming in the back with adjuvant A1 increased the mucosal IgA and IgG1 responses compared to neck priming, while the local IgG2a levels were decreased. The reverse was true for adjuvant A2. Back versus neck priming with this latter adjuvant decreased the mucosal IgG1 response, while local IgG2a levels were increased. The different lymphatic drainages of the two sites of parenteral immunization may explain these differences, due to the targeting of particular lymphoid inductive sites. Some of these sites may represent crossroads between systemic and mucosal immunity.