Greetings, I am trying to use nlme to model a large data set of pharmacokinetic concentrations with sparse data per cluster. The base model is a one compartment model with first order absorption. The program runs but the PNLS step never converges. The parameter estimates are reasonable. The plot of the individual level residuals is pretty reasonable and the plot of the residuals from the population model is ok but not great. My questions are: 1) I know the PNLS step starts and updates the fixed parameters and random effects. Step 2 is the LME step and it updates the interpatient variance. Does the LME step include both the EM algorithm and a Newton- Raphson ms step? 2) I set Maxiter=500 interations and I get convergence on what I think is the LME step but PNLS step never converges. Any suggestions on what I might do to achieve convergence would be very much appreciated. Thank you, Suzette ================================Suzette Blanchard, Ph.D. Research Scientist Frontier Science Foundation 1244 Boylston St. Suite 303 Chestnut Hill, MA 02467 Email: suzette at sdac.harvard.edu Phone: (617) 632-2007 Fax: (617) 632-2001