A series of 20 peptide analogs of (des-Glu1)conotoxin GI were prepared by solid phase synthesis. The peptides were tested for their abilities to inhibit contractions in the mouse-diaphragm-with-phrenic-nerve assay. (Des-Glu1)conotoxin has an IC50 of 2.7 x 10(-7) M in this assay. Results from this assay show that total loss of paralytic activity occurs when Pro is replaced by Gly, Tyr by D-Tyr, or Gly by D-Phe. In most cases loss or change in length of one of the disulfide rings eliminates paralytic activity except with compound 17, which is weakly active, IC50 = 7.0 x 10(-5) M. Replacement of the Cys1-Cys6 disulfide bond with an amide bond (compound 9) greatly lowers paralytic activity, IC50 = 3.7 x 10(-5) M.