The lettrine package depends on the font having the character X in order to perform its calculations; and this font, it seems, does not have the character. The lettrine macro in question is \LettrineFont. It constructs a box containing the X in a given font and then measures its height. For this font and this character, LuaTeX reports a box height of 0 pt. A following integer division then fails.
Strictly speaking, the lettrine assumption is fair and the font is at fault for not providing even a minimal set of characters. If you still want to use this font, the easiest way is to modify \LettrineFont to use a character that exists in this font, such as O:
\documentclass{minimal}
\usepackage{lettrine}
\usepackage{fontspec,xunicode}
\usepackage{etoolbox}
\newfontfamily\EBLettrineFont{EBGaramondInitialsF2}
\renewcommand{\LettrineFontHook}{\EBLettrineFont}
\patchcmd{\LettrineFont}{\selectfont X}{\selectfont O}{}{%
\GenericWarning{}{Patching \protect\LettrineFont\space failed}}
\begin{document}
\lettrine{T}{his} is a test
\end{document}
XeTeX, unlike LuaTeX, returns the height of nonexistent X as 8.10722 pt with this example code, and therefore division by zero does not occur.
lualatex(beta-0.65.0-2011041019 (rev 4033) from Ubuntu's TL2009) I get another error, I getXeTeX is required to compile this document.. – N.N. Aug 23 '11 at 11:28