Although in vitro evidence suggests two c-Jun N-terminal kinase (JNK) kinases, MKK4 and MKK7, transactivate JNK, in vivo confirmation is incomplete. In fact, JNK deficiency may differ from the composite deficiency of MKK4 and MKK7 in Drosophila and mice. Recently, the Caenorhabditis elegans homolog of human JNK,
jnk-1, and two MKK-7s,
mek-1 and
jkk-1, were cloned. Here we characterize
jnk-1, which encodes two isoforms JNK-1 alpha and JNK-1 beta. A null allele,
jnk-1(
gk7), yielded worms with defective body movement coordination and modest mechanosensory deficits. Similarly to
jkk-1 mutants, elimination of GABAergic signals suppressed the
jnk-1(
gk7) locomotion defect. Like
mek-1 nulls,
jnk-1(
gk7) showed copper and cadmium hypersensitivity. Conditional expression of JNK-1 isoforms rescued these defects, suggesting that they are not due to developmental errors. While
jkk-1 or
mek-1 inactivation mimicked
jnk-1(
gk7) locomotion and heavy metal stress defects, respectively,
mkk-4 inactivation did not, but rather yielded defective egg laying. Our results delineate at least two different JNK pathways through
jkk-1 and
mek-1 in C. elegans, and define interaction between MKK7, but not MKK4, and JNK.