Response surface modelling is proposed as an approach to the estimation of uncertainties associated with derivatisation, and is compared with a kinetic study. Fatty acid methyl ester formation is used to illustrate the approach, and kinetic data for acid-catalysed methylation and base-catalysed transesterification are presented. Kinetic effects did not lead to significant uncertainty contributions under normal conditions for base-catalysed transesterification of triglycerides. Uncertainties for acid-catalysed methylation with BF3 approach significance, but could be reduced by extending reaction times from 3 to 5 min. Non-linearity is a common feature of response surface models for derivatisation and compromised first-order estimates of uncertainty; it was necessary to include higher order differential terms in the uncertainty estimate. Simulations were used to examine the general applicability of the approach and to study the effects of poor precision and of change of response surface model. It is concluded that reliable uncertainty estimates are available only when the model is statistically significant, robust, representative of the underlying behaviour of the system, and forms a good fit to the data; arbitrary models are not generally suitable for uncertainty estimation. Where statistically insignificant effects were included in models, they gave negligible uncertainty contributions.