Here, we report the isolation and characterization of zebrafish activin receptor-like kinase-8 (zALK-8), a novel type I serine/threonine (ser/thr) kinase receptor of the transforming growth factor beta (TGF-beta) family. zALK-8 is novel, in that it contains an extracellular domain that is quite distinct from that of previously identified ALK receptors 1 through 7. Analysis of the predicted amino acid sequence of the 506 amino acid zALK-8 receptor reveals an ser/thr kinase domain characteristic of type I TGF-beta family member receptors. zALK-8, therefore, is a traditional type I ser/thr kinase receptor of the TGF-beta family, but it may exhibit novel ligand-binding activities. The developmental expression of zALK-8 mRNA was examined by wholemount in situ hybridization analysis using a probe from the 3'-untranslated sequence of zALK-8, which does not cross react with other members of the highly conserved TGF-beta receptor family. zALK-8 mRNA is present as a maternal message that is expressed ubiquitously before the start of zygotic transcription. By 16 hr postfertilization (hpf), zALK-8 mRNA is still expressed fairly evenly throughout the embryo. In 24-hpf embryos, zALK-8 mRNA is expressed predominantly in the developing eye and neural structures. By 48 hpf, zALK-8 mRNA is faintly detectable as a diffuse signal throughout the head. zALK-8 mRNA is not detectable by this method in 72-hpf or 96-hpf embryos. Northern analysis of zALK-8 mRNA in poly(A+) mRNA isolated from 6-9 hpf embryos detects a major transcript of 3.6 kb and a minor transcript of 4.3 kb. zALK-8 mRNA expression correlates well with known functions of TGF-beta family members as early axial patterning and mesoderm-inducing growth factors and as potent growth and differentiation factors in craniofacial development.