The venom compositions of Crotalus adamanteus and C. horridus differed drastically, consistent with their respective type I and type II classifications. The toxin-gene expression of C. adamanteus was dominated by snake-venom metalloproteinases (SVMPs), C-type lectins (CTLs), snake-venom serine proteinases (SVSPs), and a single, high-abundance myotoxin-A (MYO). These toxin classes, with the exception of SVSPs, were barely detectable in the venom-gland transcriptome of C. horridus, despite a similar number of reads mapping to toxins. The venom-gene expression of C. horridus was instead dominated by SVSPs, phospholipases A2 (PLA2s), and a single gene encoding bradykinin-potentiating and C-type natriuretic peptides (BPP). For both species, unique toxin sequences were grouped into clusters showing less than 1% nucleotide divergence. The other toxin-class abbreviations are as follows: cysteine-rich secretory protein, CRISP; and L-amino acid oxidase, LAAO.