The N-15 chemical shift anisotropy, Delta sigma, is reported for 81 well-ordered backbone amide sites in the Escherichia coli enzyme ribonuclease H. The values of Delta sigma were determined from N-15 relaxation rate constants measured at static magnetic field strengths of 11.7, 14.1, and 18.7 T; the data analyzed included both autorelaxation rate constants and H-1-N-15 dipolar/N-15 chemical shift anisotropy relaxation interference rate constants. For this data set, the values of ha an approximately Gaussian distributed with a mean of -172 +/- 13 ppm. The standard deviation of the site-to-site variation of the chemical shift anisotropy is 5.5 ppm and a 95% confidence limit for this variation is 9.6 ppm. The site-to-site variation in the chemical shift anisotropy is similar to the variation observed in solid state NMR studies of specifically labeled polypeptides. Variability in the value of Delta sigma becomes a significant factor in the interpretation of spin relaxation rate constants at 18.7 T, but is less significant at lower field strengths, for the precision of relaxation data presently achievable by solution NMR. Ribonuclease H is the second protein for which an extensive set of Delta sigma values is available. Comparison of results for ribonuclease H with results reported for well-ordered sites in ubiquitin (Fushman, D.; Tjandra, N.; Cowburn, D. J. Anl. Chem. Sec. 1998, 120, 10937-10952) reveals differences primarily in the larger number of statistically significant values far from the mean in ubiquitin.