We compared four equations for estimating intrathecal IgG synthesis (Tibbling and Link IgG index (T/L), Schuller and Sagar (S/S), Reiber and Felgenhauer (R/F), and Tourtellotte (T) equations) using data from chronic progressive MS patients. For normal albumin leakage (AL) (<75 mg/day - intact BBB), T ( r = 0.15) and R/F ( r = 0.10) showed comparable positive correlations with trans-BBB AL, T/L ( r = −0.10) was negative and S/S was uncorrelated ( r = 0.05). For abnormal AL ( ≧ 75 mg/day ), the R/F ( r = −0.24), S/S ( r = −0.37) and the T/L ( r = −0.22) equations overcorrected, whereas the T ( r = 0.07) equation values did not correlate with AL. The albumin index and trans-BBB albumin leakage rate formulae gave essentially identical estimates of BBB leakage ( r = 0.99, P = 0.0001). We conclude that in chronic progressive MS patients the R/F, T/L and S/S formulae overcompensate for large abnormal T-BBB albumin leakage rates. The T formula corrected best for IgG transudate at high AL rate values in MS.