A new procedure based on the statistical method of "variable selection" is used to predict the secondary structure of proteins from circular dichroism spectra. Variable selection adds the flexibility found in the Provencher and Glöckner method (S. W. Provencher and J. Glöckner, 1981, Biochemistry 20, 33-37) to the method of Hennessey and Johnson (J. P. Hennessey and W. C. Johnson, 1981, Biochemistry 20, 1085-1094). Two analytical methods are presented for choosing a solution from the series generated by the Provencher and Glöckner method, and this improves the technique. All three methods are compared and it is shown that both the variable selection method and the improved Provencher and Glöckner methods have equivalent reliability superior to the original Hennessey and Johnson method. For the new variable selection method, correlation coefficients calculated between X-ray structure and predicted secondary structures for data measured to 178 nm are: 0.97 for alpha-helix, 0.75 for beta-sheet, 0.50 for beta-turn, and 0.89 for other structures. Although the variable selection method improves the analysis of circular dichroism data truncated at 190 nm, data measured to 178 nm gives superior results. It is shown that improving the fit to the measured CD beyond the accuracy of the data can result in poorer analyses.